Gastroschisis is a congenital abdominal wall defect, thought by many to represent a disruption in intrauterine blood flow, where there is herniation of abdominal organs. Dietary intake is an important environmental factor that has been implicated in the development of many diseases. Omega-6 polyunsaturated fatty acids (PUFAs) are nutrients that are substrates for eicosanoid and cytokine synthesis and prone to oxidation, and play a role in modulating inflammation, immune function, and vascular system development. This pilot case-control study explored the association of dietary intake of the omega-6 PUFA linoleic acid with risk of gastroschisis. Between 2008 and 2011, we recruited 13 pregnant women in mid-gestation who were referred to the UCSD Prenatal Center for evaluation of an abnormal alpha-fetoprotein (AFP) test and subsequently identified as carrying a baby with gastroschisis. Nine controls were selected from a false positive AFP or from the UCSD prenatal clinic. Maternal dietary intake was collected via repeated food record during the last 20 weeks of gestation. Logistic regression was used to test the association between dietary intake of linoleic acid and odds of gastroschisis. Dietary intake of linoleic acid was associated with increased odds of gastroschisis (OR = 1.72; 95% CI: 1.08, 2.74; P = 0.02). A higher maternal intake of omega-6 PUFAs may increase the risk of having a baby with gastroschisis. The mechanism by which this occurs may be via inflammatory processes and oxidative stress leading to a vascular disruption. More research is needed including studies investigating integrated markers of PUFA status or inflammatory markers. © 2012 Wiley Periodicals, Inc.